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      Amino acid PET and MR perfusion imaging in brain tumours

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          Abstract

          Purpose

          Despite the excellent capacity of the conventional MRI to image brain tumours, problems remain in answering a number of critical diagnostic questions. To overcome these diagnostic shortcomings, PET using radiolabeled amino acids and perfusion-weighted imaging (PWI) are currently under clinical evaluation. The role of amino acid PET and PWI in different diagnostic challenges in brain tumours is controversial.

          Methods

          Based on the literature and experience of our centres in correlative imaging with PWI and PET using O-(2-[ 18F]fluoroethyl)- l-tyrosine or 3,4-dihydroxy-6-[ 18F]-fluoro- l-phenylalanine, the current role and shortcomings of amino acid PET and PWI in different diagnostic challenges in brain tumours are reviewed. Literature searches were performed on PubMed, and additional literature was retrieved from the reference lists of identified articles. In particular, all studies in which amino acid PET was directly compared with PWI were included.

          Results

          PWI is more readily available, but requires substantial expertise and is more sensitive to artifacts than amino acid PET. At initial diagnosis, PWI and amino acid PET can help to define a site for biopsy but amino acid PET appears to be more powerful to define the tumor extent. Both methods are helpful to differentiate progression or recurrence from unspecific posttherapeutic changes. Assessment of therapeutic efficacy can be achieved especially with amino acid PET, while the data with PWI are sparse.

          Conclusion

          Both PWI and amino acid PET add valuable diagnostic information to the conventional MRI in the assessment of patients with brain tumours, but further studies are necessary to explore the complementary nature of these two methods.

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          Most cited references124

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          MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients.

          Standard therapy for glioblastoma (GBM) is temozolomide (TMZ) administration, initially concurrent with radiotherapy (RT), and subsequently as maintenance therapy. The radiologic images obtained in this setting can be difficult to interpret since they may show radiation-induced pseudoprogression (psPD) rather than disease progression. Patients with histologically confirmed GBM underwent radiotherapy plus continuous daily temozolomide (75 mg/m(2)/d), followed by 12 maintenance temozolomide cycles (150 to 200 mg/m(2) for 5 days every 28 days) if magnetic resonance imaging (MRI) showed no enhancement suggesting a tumor; otherwise, chemotherapy was delivered until complete response or unequivocal progression. The first MRI scan was performed 1 month after completing combined chemoradiotherapy. In 103 patients (mean age, 52 years [range 20 to 73 years]), total resection, subtotal resection, and biopsy were obtained in 51, 51, and 1 cases, respectively. MGMT promoter was methylated in 36 patients (35%) and unmethylated in 67 patients (65%). Lesion enlargement, evidenced at the first MRI scan in 50 of 103 patients, was subsequently classified as psPD in 32 patients and early disease progression in 18 patients. PsPD was recorded in 21 (91%) of 23 methylated MGMT promoter and 11 (41%) of 27 unmethylated MGMT promoter (P = .0002) patients. MGMT status (P = .001) and psPD detection (P = .045) significantly influenced survival. PsPD has a clinical impact on chemotherapy-treated GBM, as it may express the glioma killing effects of treatment and is significantly correlated with MGMT status. Improvement in the early recognition of psPD patterns and knowledge of mechanisms underlying this phenomenon are crucial to eliminating biases in evaluating the results of clinical trials and guaranteeing effective treatment.
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            Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging.

            Sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of conventional MR imaging in predicting glioma grade are not high. Relative cerebral blood volume (rCBV) measurements derived from perfusion MR imaging and metabolite ratios from proton MR spectroscopy are useful in predicting glioma grade. We evaluated the sensitivity, specificity, PPV, and NPV of perfusion MR imaging and MR spectroscopy compared with conventional MR imaging in grading primary gliomas. One hundred sixty patients with a primary cerebral glioma underwent conventional MR imaging, dynamic contrast-enhanced T2*-weighted perfusion MR imaging, and proton MR spectroscopy. Gliomas were graded as low or high based on conventional MR imaging findings. The rCBV measurements were obtained from regions of maximum perfusion. Metabolite ratios (choline [Cho]/creatine [Cr], Cho/N-acetylaspartate [NAA], and NAA/Cr) were measured at a TE of 144 ms. Tumor grade determined with the three methods was then compared with that from histopathologic grading. Logistic regression and receiver operating characteristic analyses were performed to determine optimum thresholds for tumor grading. Sensitivity, specificity, PPV, and NPV for identifying high-grade gliomas were also calculated. Sensitivity, specificity, PPV, and NPV for determining a high-grade glioma with conventional MR imaging were 72.5%, 65.0%, 86.1%, and 44.1%, respectively. Statistical analysis demonstrated a threshold value of 1.75 for rCBV to provide sensitivity, specificity, PPV, and NPV of 95.0%, 57.5%, 87.0%, and 79.3%, respectively. Threshold values of 1.08 and 1.56 for Cho/Cr and 0.75 and 1.60 for Cho/NAA provided the minimum C2 and C1 errors, respectively, for determining a high-grade glioma. The combination of rCBV, Cho/Cr, and Cho/NAA resulted in sensitivity, specificity, PPV, and NPV of 93.3%, 60.0%, 87.5%, and 75.0%, respectively. Significant differences were noted in the rCBV and Cho/Cr, Cho/NAA, and NAA/Cr ratios between low- and high-grade gliomas (P <.0001,.0121,.001, and.0038, respectively). The rCBV measurements and metabolite ratios both individually and in combination can increase the sensitivity and PPV when compared with conventional MR imaging alone in determining glioma grade. The rCBV measurements had the most superior diagnostic performance (either with or without metabolite ratios) in predicting glioma grade. Threshold values can be used in a clinical setting to evaluate tumors preoperatively for histologic grade and provide a means for guiding treatment and predicting postoperative patient outcome.
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              Single-Fraction Versus Multifraction (3 × 9 Gy) Stereotactic Radiosurgery for Large (>2 cm) Brain Metastases: A Comparative Analysis of Local Control and Risk of Radiation-Induced Brain Necrosis.

              To investigate the local control and radiation-induced brain necrosis in patients with brain metastases >2 cm in size who received single-fraction or multifraction stereotactic radiosurgery (SRS); factors associated with clinical outcomes and the development of brain radionecrosis were assessed.
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                Author and article information

                Contributors
                0049-2461-61-5900 , k.j.langen@fz-juelich.de
                Journal
                Clin Transl Imaging
                Clin Transl Imaging
                Clinical and Translational Imaging
                Springer Milan (Milan )
                2281-5872
                2281-7565
                13 March 2017
                13 March 2017
                2017
                : 5
                : 3
                : 209-223
                Affiliations
                [1 ]ISNI 0000 0001 2297 375X, GRID grid.8385.6, Institute of Neuroscience and Medicine (INM-3, INM-4), , Forschungszentrum Jülich, ; Jülich, Germany
                [2 ]ISNI 0000 0001 0728 696X, GRID grid.1957.a, Departments of Nuclear Medicine and Neurology, , RWTH Aachen University Clinic, ; Aachen, Germany
                [3 ]GRID grid.7841.a, Unit of Nuclear Medicine, Department of Surgical and Medical Sciences and Translational Medicine, , Sapienza University of Rome, ; Rome, Italy
                [4 ]ISNI 0000 0001 0423 4662, GRID grid.8515.9, Nuclear Medicine and Molecular Medicine Department, , University Hospital of Lausanne, ; Lausanne, Switzerland
                [5 ]JARA–Jülich Aachen Research Alliance, Jülich, Germany
                [6 ]ISNI 0000 0004 1936 7857, GRID grid.1002.3, Monash Institute of Medical Engineering, Department of Electrical and Computer Systems Engineering, and Monash Biomedical Imaging, School of Psychological Sciences, , Monash University, ; Melbourne, VIC Australia
                [7 ]ISNI 0000 0000 8580 3777, GRID grid.6190.e, Department of Neurology, , University of Cologne, ; Cologne, Germany
                [8 ]ISNI 0000 0000 8580 3777, GRID grid.6190.e, Center of Integrated Oncology (CIO), , University of Cologne and Bonn, ; Cologne, Germany
                Author information
                http://orcid.org/0000-0003-1101-5075
                Article
                225
                10.1007/s40336-017-0225-z
                5487907
                28680873
                f0c0fe63-c7e3-461b-a97e-966602299c0b
                © Italian Association of Nuclear Medicine and Molecular Imaging 2017
                History
                : 17 December 2016
                : 28 February 2017
                Categories
                Expert Review
                Custom metadata
                © Italian Association of Nuclear Medicine and Molecular Imaging 2017

                amino acid pet,18f-fet,18f-fdopa,perfusion-weighted mri,relative cerebral blood volume (rcbv),brain tumours

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